The work which is proposed represents a continuation and extension of current projects. These are as follows: (i). The CO2 signal in arterial blood. We have developed a rapidly-responding CO2 sensor using mass spectrometry and with this, we have been ableto characterize respiratory fluctuations of PaCO2 and to demonstrate a decay of PaCO2 with time in pulmonary post-capillary blood. Although we have been able to show how the magnitude of this decay is affected by various manoeuvres and to indicate what the physiological consequences of this decay might be, the mechanism remains obsure: and in the future experiments. we shall be studying this in detail by determining the kinetics of the carbamino reaction in vitro. (ii) Studies on carotid body chemoreception. We have been able to show in the adult cat that the chemoreception of hypoxia appears to involve beta-adrenergic receptors and this suggests that noradrenaline, released from Type I cells, may be excitatory transmitter. The mechanisms involved in this action will be explored in detail. In parallel, studies, we have been able to show that although dopamine can be detected in the carotid body of the 110 day sheep feotus and that its concentration increases with gestational age, noradrenaline only appears a very few days before natural term but then increases very rapidly in concentration over birth and in the first post-natal days. The implication of this observation will be studied in detail in the near future: but already it provides an explanation of the relative absence of chemoreceptor activity in the mature foetus and the abundance of activity in the newborn. (iii) pH sensitivity of medullary neurones. We have developed a syatem for the measurement of inTra- or extra-cellular activity in cells in transverse slices of rat's medulla oblongate in vitro. So far, it has been possible to show that cells in respiratory areas such as the nucleus of the solitaty tract, nucleus ambiguus or in other areas such as the inferior olive, motor nucleus of X, vestibular nucleus respond to a fa-1 in pH or a rise of PCO2 of the superfusing solution with either hyperpolarization or a reduction in discharge frequency. The significance of this is being studied further.